From M.A. Bozarth (1994). Pleasure systems in the brain.
In D.M. Warburton (ed.), Pleasure: The politics and the reality
(pp. 5-14 + refs). New York: John Wiley & Sons. (Note: Minor typographical
errors appearing in the published version have been corrected.)

Pleasure Systems in the Brain

Michael A. BozarthBehavioral Neuroscience ProgramDepartment of PsychologyState University of New York at BuffaloBuffalo, New York 14260-4110 USA

Neurological research has identified a biological mechanism mediating
behavior motivated by events commonly associated with pleasure in humans.
These events are termed "rewards" and are viewed as primary factors governing
normal behavior. The subjective impact of rewards (e.g., pleasure) can
be considered essential (e.g., Young, 1959) or irrelevant (e.g., Skinner,
1953) to their effect on behavior, but the motivational effect of rewards
on behavior is universally acknowledged by experimental psychologists.

Motivation & Reward

Motivation can be considered under two general rubrics預ppetitive and aversive
motivation. Appetitive motivation concerns behavior directed toward
goals that are usually associated with positive hedonic processes; food,
sex, and wine are three such goal objects. Aversive motivation involves
escaping from some hedonically unpleasant condition; the pain from a headache,
the chill from a cold winter night are among the list of conditions that
give rise to aversive motivation. The notion that hedonic mechanisms might
provide direction to behavior can be traced at least to the Greeks (e.g.,
Epicures); Spencer (1880) formalized this notion into psychological theory
and suggested that two fundamental forces governed motivation--pleasure
and pain. Troland (1928) suggested that pleasure was associated with beneception,
events that contributed to the survival of the organism (or species) and
thus 'benefited' the organism from an evolutionary biology perspective;
pain was suggested to be associated with nociception, events that had undesirable
consequences for the organism. This schema容mphasizing hedonic processes
in the regulation of behavior様ost favor with the advance of the Freudian
and later behavioristic schools, although variations on this theme have
occasionally resurfaced among motivational psychologists (e.g., Bindra,
1969; Young, 1959).

Behaviorism traditionally rejects the notion that subjective experience
has a critical role in determining behavior. Specifically, behaviorism
describes the relationship between behavior and external factors governing
that behavior without reference to internal states, albeit it does help
to have a hungry (i.e., food deprived) rat when studying the ability of
food to serve as a reward. Behaviorism, or more properly operant conditioning
theory, postulates three fundamental principles of behavior用ositive reinforcement,
negative reinforcement, and punishment. Positive reinforcement describes
the situation where presentation of some stimulus event (e.g., food) increases
the probability or frequency of the behavior it follows. Negative reinforcement
describes the situation where the termination of some stimulus event (e.g.,
electric shock) increases the probability or frequency of the behavior
its termination follows. Both positive and negative reinforcers increase
behavioral responses; they differ in the temporal relationship between
the behavior and the reinforcing event用ositive reinforcers follow the
behavior they reinforce, while negative reinforcers precede the behavior
they reinforcement. (In colloquial terms, the organism is said to work
to receive a positive reinforcer and to work to escape from a negative
reinforcer.) Punishment is the third general principle of operant conditioning.
Punishment describes the situation where presentation of an aversive
stimulus following a behavior decreases the probability or frequency of
that behavior. Unlike reinforcers, punishers suppress behavior. Radical
behaviorism describes the effects of reinforcement and punishment on behavior
devoid of their subjective impact. Indeed, the emotional states associated
with reinforcement and punishment are usually viewed as the result
of behavioral conditioning and not a cause of behavior.

In general, events that serve as positive reinforcers produce approach
behavior defined as appetitive motivation. Events that serve as negative
reinforcers or punishers produce withdrawal behavior defined as aversive
motivation. Positive reinforcement is usually associated with a pleasant
hedonic impact (and hence frequently termed reward connoting this
pleasant affective component), while negative reinforcement and punishment
are usually associated with an unpleasant hedonic impact. Whether the subjective
experience of reward (viz., pleasure) plays an important role in determining
behavior is moot for the present discussion. The same principles apply
whether the emotional impact of a reward precedes or follows the behavioral
response. Furthermore, events that serve as positive reinforcers in humans
and other animals are generally described by humans as pleasant; thus,
there is an intimate association between reward and pleasure despite controversy
regarding the role of the subjective experience of pleasure in determining
behavior.

A Biological Basis of Appetitive Motivation and Reward

Physiological psychology research has identified separate but interactive
neural pathways mediating reward and aversion (i.e., functioning as positive
and negative reinforcement systems, respectively). Direct activation of
brain reward mechanisms through electrical and chemical stimulation provides
a tool for elucidating these neural systems. During the past four decades,
considerable knowledge has been gained regarding the anatomical and neurochemical
basis of these pathways. This brief presentation addresses only brain mechanisms
involved in positive reinforcement because they are closely identified
with pleasure in humans and because they underlie the primary process governing
much of normal behavior.

Reward Substrate Identified by Electrical Brain Stimulation

Olds and Milner (1954) first identified brain sites where direct electrical
stimulation is reinforcing. Laboratory animals will lever press at high
rates (> 6,000 times per hour) to obtain brief stimulation pulses to certain
brain regions. The reinforcement from direct electrical activation of this
reward substrate is more potent than other rewards, such as food or water.
The potency of this electrical stimulation is most dramatically illustrated
in a classic experiment where the subjects suffered self-imposed starvation
when forced to make a choice between obtaining food and water or electrical
brain stimulation (Routtenberg & Lindy, 1965). A second distinguishing
feature of reward from electrical brain stimulation is the lack of satiation;
animals generally respond continuously, taking only brief breaks from lever
pressing to obtain the electrical stimulation. These two features (i.e.,
super-potent reward and lack of satiation) are important characteristics
of direct activation of brain reward mechanisms.

Initial work suggested that a number of brain regions could produce
rewarding effects, but many of these seemingly diverse stimulation sites
were quickly linked through a common neural pathway葉he medial forebrain
bundle (Olds, 1977). Although it is true that activation of other brain
systems can produce rewarding effects, activation of the medial forebrain
bundle as it courses through the lateral hypothalamus to the ventral tegmentum
produces the most robust rewarding effects. And several neurotransmitters
may be involved in the rewarding effects from various electrode placements,
but dopamine appears to be the neurotransmitter essential for reward from
activation of the medial forebrain bundle system (see Fibiger & Phillips,
1979; Wise, 1978). The neuroanatomical elements of rewarding stimulation
have been identified using electrophysiological and neurochemical techniques:
electrical stimulation activates a descending component of the medial forebrain
bundle which is synaptically coupled at the ventral tegmentum to the ascending
mesolimbic dopamine system. Rewarding electrical stimulation thus activates
a circuitous reward pathway, first involving a descending medial forebrain
bundle component and then involving the ascending mesolimbic dopamine pathway
(Bozarth, 1987a; Wise, & Bozarth, 1984). The terms mesolimbic
and ventral tegmental dopamine system are used interchangeably in
this context, both denoting the same dopamine system involved in reward
and motivation.

Research with laboratory animals generally uses an operant conditioning
perspective when studying reward processes (viz., without reference to
possible subjective effects), but research in human subjects has revealed
that comparable electrical brain stimulation is associated with profoundly
pleasurable effects (e.g., Heath, 1964). Indeed, some experimental subjects
liken the effect of electrical brain stimulation to intense sexual orgasm,
and anecdotal reports suggest that human subjects have developed a strong
romantic attraction to the researchers performing the experiments. For
obvious ethical reasons, research with human subjects has been very limited.
But the available data suggest that the principles learned from animal
experimentation are valid for human subjects; studies of electrical stimulation
of reward pathways in humans provide direct evidence that stimulation that
is reinforcing in animals is both reinforcing and intensely pleasurable
in humans.

Reward Substrate Identified by Chemical Brain Stimulation

Another approach to studying brain reward systems is to determine the neurochemical
coding of these pathways. This can be accomplished by identifying the neurochemical
mechanisms whereby various drugs serve as rewards following either systemic
or intracranial administration. Essentially, reinforcing drugs can be used
as tools for studying brain reward mechanisms in much the same manner as
electrical stimulation. Experimental procedures have been developed where
animals can lever press to obtain various drug rewards (see Bozarth, 1987b).

Some drugs delivered intravenously can serve as rewards. Most drugs
that are self-administered by humans are also self-administered by laboratory
animals. The most potent drug rewards include the psychomotor stimulants
(e.g., amphetamine, cocaine) and the opiates (heroin, morphine). These
drugs are self-administered by laboratory animals that have surgically
implanted intravenous catheters. Animals quickly learn to press a lever
to intravenously self-administer drugs such as cocaine and heroin. This
experimental preparation provides an animal model of human drug-taking
behavior and hence a method to study the reinforcing properties of drugs;
this reinforcing drug-action forms the basis for drug addiction in humans
(see Bozarth, 1987b, 1990). It is important to note that addiction
is defined as a behavioral syndrome where a drug seems to exert extreme
control over the individual's behavior and is not defined by physiological
withdrawal reactions such as those accompanying abstinence from some drugs.
Drug use is seen as developing along a continuum, beginning with casual/recreational
use where the drug has a modest influence on behavior to the extreme condition
(i.e., addiction) where the drug use seems to dominate the individual's
behavior (see Bozarth, 1990).

Reward from psychomotor stimulants and from opiates appears to involve
activation of the same brain reward system as that activated by electrical
stimulation. Dopamine is the neurotransmitter most consistently linked
with reward from these drugs, and the ventral tegmental dopamine system
has been specifically implicated in psychomotor stimulant and opiate rewards.
Other drugs that may serve as reinforcers (e.g., alcohol, barbiturates,
caffeine, marijuana, nicotine) also activate the ventral tegmental dopamine
system, although the data suggesting this activation is critical for their
reinforcing effects are not conclusive. Furthermore, abstinence from cocaine
or from morphine after repeated administration may decrease dopamine levels
in this brain system (Bozarth, 1989; Rossetti, Hmaidan, & Gessa, 1992);
this diminished dopamine function may be related to the intense craving
associated with withdrawal in drug dependent humans. The subjective experience
of craving is probably related to relapse into drug-taking behavior following
abstinence and therefore is an important factor in drug addiction.

Integrative Aspects of the Ventral Tegmental "Reward" System

Research has progressed to where several distinct rewarding events can
be explained by their abilities to activate a common brain reward mechanism:
electrical brain stimulation reward, psychomotor stimulant reward, and
opiate reward all appear to involve activation of the ventral tegmental
dopamine system (Bozarth, 1987a; Wise & Bozarth, 1984). Several other
drug rewards, such as alcohol and nicotine, may also involve activation
of this brain pathway. This has lead to the assertion that various addictive
drugs share the common feature of activating the same brain reward system
and this action has been related to their appetitive motivational effects
(Wise & Bozarth, 1987). This theoretical perspective deviated sharply
from prevailing thought in that (i) it suggested a common neural basis
for two distinctively different pharmacological drug classes (i.e., psychomotor
stimulants and opiates) and (ii) it suggested that appetitive motivation
rather than aversive motivation (such as that associated with physical
dependence and overt withdrawal reactions) motivated drug-taking behavior
and addiction. From this perspective, addictive drugs are seen to pharmacologically
activate brain reward mechanisms involved in the control of normal behavior
(see Bozarth, 1990; Wise & Bozarth, 1987). Thus, addictive drugs may
be used as tools to study brain mechanisms involved in normal motivational
and reward processes.

Other, natural rewards can be modulated by the activity of this system:
feeding can be elicited (Hamilton & Bozarth, 1988), sexual behavioral
can be aroused (Mitchell & Stewart, 1990), and maternal behavior can
be facilitated (Thompson & Kristal, 1992) by opiate activation of this
reward system. The origin of the ventral tegmental dopamine system (i.e.,
ventral tegmentum) appears to provide an important neurochemical interface
where exogenous opiates (e.g., heroin, morphine) and endogenous opioid
peptides (e.g., endorphins, enkephalins) can activate a brain mechanism
involved in appetitive motivation and reward. These and other empirical
findings are consistent with the notion that the ventral tegmental dopamine
system may serve as an appetitive motivation system for diverse behaviors.
This is not to suggest that all motivational effects of these rewards emanate
from this single brain system, but rather this dopamine system represents
one important mechanism for the control of both normal and pathological
behaviors. (For a more technical review, see Bozarth, 1987a, 1991).

The hypothesized activation of the ventral tegmental reward system by
endogenous opioid peptides can offer an explanation of seemingly paradoxical
behavior葉he voluntary self-infliction of stress or pain. Events normally
considered stressful and thus aversive may activate the ventral tegmental
reward system through the release of endogenous opioid peptides induced
by the stressor. (Stress-induced release of endogenous opioid peptides
was one of the earliest identified effects for these neuromodulators.)
This could explain the attraction some individuals display to seemingly
aversive stimulation (e.g., risk-taking behavior, self-infliction of painful
stimuli). In some situations the appetitive motivational effect of these
behaviors may override the normal aversive motivational effect that usually
produces withdrawal behavior; thus in certain pathological conditions,
approach behavior indicative of appetitive motivation may be produced by
an aversive stimulus normally avoided and described as painful. This is
most likely perhaps in situations where the effects of the stress-induced
endogenous opioid peptide release out last the abrupt termination of the
painful stimulus. Also, cognitive processes may label the stressor as nonthreatening,
thereby permitting the pleasurable effects to dominate affective tone.

The Pursuit of Pleasure: When Does it Become Pathological?

Activation of brain reward systems can be considered a natural component
of normal behavior. Indeed, brain reward systems serve to direct the organism's
behavior toward goals that are normally beneficial and promote survival
of the individual (e.g., food and water intake) or the species (e.g., reproductive
behavior) as suggested by Troland's (1928) concept of beneception. The
notion that the brain influences behavior is not particularly radical for
twentieth century scientists nor is the notion that many rewards activate
such mechanisms through various sense modalities such as taste or touch.
The direct chemical activation of these reward pathways does not in itself
represent any severe departure from the normal control reward systems exert
over behavior. Inhalation of a substance (e.g., nicotine) is no less natural
than the ingestion of sugar, although the former has no direct survival
value to the organism nor to the species. But both involve activation of
brain reward mechanisms and both may be subjectively experienced as pleasurable
in humans. So what constitutes the pathological control of behavior termed
"addiction?" Certainly not the fact that a substance activates a brain
reward system nor the fact that this same system may be involved in the
potent reward produced by addictive drugs. Simple activation of brain reward
systems does not constitute addiction! Rather, the extreme control of behavior容xemplified
by a deterioration in the ability of normal rewards to govern behavior
(termed motivational toxicity)擁s the distinguishing feature of
an addiction. Some drugs quickly and uniformly exert extreme control over
behavior (e.g., cocaine, heroin), while other substances exert a much less
potent influence on behavior (e.g., moderate alcohol consumption, occasional
nicotine use). The fact that a chemical (e.g., nicotine) influences behavior
does not constitute addiction any more than the chemical reaction that
produces a taste (e.g., sugar-associated sweetness) which influences behavior
constitutes addiction.

Motivational toxicity is apparent when rewards normally effective in
influencing behavior lose their ability to motivate the organism. This
is typically seen in human drug addicts that neglect formerly potent rewards
(e.g., career, sex) and focus their behavior on the acquisition and ingestion
of drug. The neural mechanisms responsible for this disruption of the motivational
hierarchy have not been identified; one potential mechanism involves decreased
dopaminergic function following chronic drug use (see Bozarth, 1989). In
a reward system with decreased dopaminergic function, natural rewards that
activate reward processes much less potently than some drug rewards (e.g.,
cocaine, heroin) may lose their abilities to engage the organism's behavior.
In contradistinction, direct pharmacological activation of a reward system
dominates the organism's motivational hierarchy at the expense of other
rewards that promote survival. The ensuing motivational toxicity distinguishes
drug addiction from simple drug activation of reward mechanisms. Motivational
toxicity may develop from neuroadaptive responses to chronic intake of
some drugs, but it is not a general property of chemical activation of
brain reward mechanisms.

Epilogue on the Role of Pleasure

Brain systems involved in what the behaviorist terms positive reinforcement
are also involved in the sensation of pleasure in humans. Although radical
behaviorism ignores the hedonic impact of positive reinforcers, the subjective
experience of pleasure is a usual concomitant of positive reinforcement.
Because humans most often describe their own behavior in terms of subjective
experience instead of the behavioristic terms of operant conditioning theory
(e.g., positive reinforcement), it is appropriate to use reward and pleasure
as descriptors of events governing human behavior. Indeed, the phrase introduced
by Olds (1956), "pleasure centers in the brain," remains generally descriptive
of the neural basis of reward, but the word center (suggesting a
single neuroanatomical focus) has been replaced by the word systems
(emphasizing multiple neural elements) as additional neural linkages have
been identified.

Appetitive motivation is most often associated with goals that have
benefited the species from an evolutionary biology perspective. Specialized
brain systems have evolved that direct the organism toward historically
beneficial goals, and these systems could be termed pleasure systems
in colloquial language. Whether the sensation of pleasure is a critical
determinant of behavior or a simple concomitant of reward activation remains
to be resolved: appetitive motivational is intimately linked with the subjective
experience of pleasure.

Much of behavior can be explained by simple processes of approaching
pleasant stimuli and avoiding painful stimuli as described by Spencer (1880)
in the nineteenth century. The ventral tegmental dopamine system is an
important neural substrate for reward, and it has a central role in regulating
appetitive motivation: several distinct rewarding events activate this
reward system, and activation of this system elicits appetitive motivation.
The ventral tegmental dopamine system, along with its various neural inputs
and outputs, can be aptly designated a "pleasure system in the brain" with
an important role regulating many normal and pathological behaviors.

Selected Bibliography

Bindra, D. (1969). A unified interpretation of emotion and
motivation. Annals of the New York Academy of Sciences159:
1071-1083.

Heath, R.G. (1964). Pleasure response of human subjects
to direct stimulation of the brain: Physiologic and psychodynamic considerations.
In R.G. Heath (ed.), The Role of Pleasure in Human Behavior (pp.
219-243). New York: Hoeber.